The objectives of the proposed project are (1) to evaluate in vivo tumorigenicity and in vitro induction of malignant transformation by selected antineoplastic drugs in clinical use; (2) to assess the cytogenetic profile of drug-induced tumors and drug transformed cells; (3) to determine the transplantability of clonal derivatives of cultured drug-induced tumor and to compare the chromosomal changes associated with each clone, and (4) to monitor the temporal in vitro cytogenetic changes in each clone and each secondary tumor. Our previous studies have confirmed the tumorigenicity of adriamycin and its ability to transform cultured BHK and mouse embryo cells. Our studies have further demonstrated that adriamycin-induced tumors or transformed cells are characterized by numerous karyotypic variations during the early stages of development. In the later stages of development, however, certain tumors or clones of transformed cells or cultured tumor cells generate chromosome markers suggestive of clonal origin. It is the scope of the project to focus on cytogenetics of drug-induced tumors as they relate to clonal aspect of neoplastic development. Emphasis will be placed on (1) karyotypic differences and similarity among clones derived from the same or different tumors; (2) the time of evaluation of specific cytogenetic markers in isolated clones and in their induced secondary tumors.